In utero undernutrition reduces diabetes incidence in non-obese diabetic mice

Aims/hypothesis Observational studies in humans suggest that low birthweight may decrease the risk of type 1 diabetes, but the mechanism is unknown. We hypothesised that antenatal undernutrition would decrease the incidence of type 1 diabetes in non-obese diabetic (NOD) mice. Materials and methods A...

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Bibliographic Details
Published in:Diabetologia 2007-05, Vol.50 (5), p.1099-1108
Main Authors: Oge, A, Isganaitis, E, Jimenez-Chillaron, J, Reamer, C, Faucette, R, Barry, K, Przybyla, R, Patti, M. E
Format: Article
Language:English
Subjects:
Absorptiometry, Photon
Age
Animals
Apoptosis
Biological and medical sciences
Birth weight
Diabetes
Diabetes Mellitus, Type 1 - epidemiology
Diabetes Mellitus, Type 1 - prevention & control
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Female
Females
Fetal Growth Retardation - physiopathology
Glucose
Health risk assessment
Histology
Homeostasis
In Situ Nick-End Labeling
Incidence
Insulin
Laboratory animals
leptin
low birth weight
Males
Malnutrition - embryology
Medical sciences
Metabolic diseases
Mice
Mice, Inbred NOD
NOD
Non-obese diabetic mice
Other nutritional diseases (malnutrition, nutritional and vitamin deficiencies...)
Pathogenesis
Pregnancy
Type 1 diabetes mellitus
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Summary:Aims/hypothesis Observational studies in humans suggest that low birthweight may decrease the risk of type 1 diabetes, but the mechanism is unknown. We hypothesised that antenatal undernutrition would decrease the incidence of type 1 diabetes in non-obese diabetic (NOD) mice. Materials and methods A 40% restriction of energy intake was applied to pregnant NOD dams from day 12.5 to day 18.5 of gestation, resulting in intrauterine growth retardation of offspring. All mice were fed a standard diet after weaning. Control and undernourished female offspring were followed to assess diabetes incidence. Male NOD mice were treated with cyclophosphamide to accelerate development of diabetes. Glucose homeostasis, body composition and pancreatic histology were compared in control and undernourished offspring. Results Mean birthweight was lower in undernourished than in control mice (p = 0.00003). At 24 weeks of age, the cumulative incidence of spontaneous diabetes in female mice was 73% in control and 48% in undernourished mice (p = 0.003). In cyclophosphamide-treated male mice, antenatal undernutrition also tended to reduce the development of diabetes (p = 0.058). Maternal leptin levels were lower in undernourished dams on day 18.5 of pregnancy (p = 0.039), while postnatal leptin levels were significantly higher in undernourished offspring at 4, 20 and 27 weeks of life (p < 0.05). Beta cell mass was similar in both groups (control = 0.4 mg; undernourished = 0.54 mg; p = 0.24). Histological evidence of apoptosis at 20 weeks was greater in control than in undernourished mice (control = 6.3 ± 1.4%; undernourished = 4.2 ± 0.3%, p = 0.05). Conclusions/interpretation Antenatal undernutrition reduces the incidence of diabetes in NOD mice, perhaps via alterations in apoptosis.
ISSN:0012-186X
1432-0428
DOI:10.1007/s00125-007-0617-0